Unsymmetrical quaternary ammonium alkyl sulfates



Fatenteci fsegai. 2&1, E g? UNSYMMETRICAL QUATERNARY AMltIO- NIUM ALKYLSULFATES Joseph B. Niederl, Brooklyn, N. Y., William F. Hart, Easton,Pa., and Martin E. McGreal, Sommersworth, N. IL, assignors to J. B.Niederl & Associates, Inc., New York, N. Y., a corporation of New YorkNo Drawing. Application July 30, 1948, Serial No. 41,728

13 Claims. (Cl. 260-2471) This invention relates to unsymmetricalquaternary ester-salts of morpholine and thiamorpholine and to theprocess by which they are produced.

This application carries forward work done in connection with certain ofthe compounds described in our Patent No. 2,380,325 relating toAsymmetric Quaternary Ester-Salts of Morpholine, issued July 10, 1945.The present invention differs, however, in both the process as well asthe types of compounds produced.

As to the process, in the present invention a more direct method isused. Instead of first preparing a reactive quaternary ammonium halideand reacting this halide with appropriate metal salts of a mono-alkylsulfate, in the present invention a tertiary amine is reacted directlywith an unsymmetrical dialkyl sulfate as follows:

Although in the present invention the alkyl radical in the anionic partof the molecule is different from any radicals in the cationic part ofthe molecule, all the radicals in linked to the quaternary nitrogen atomneed not to be different, which is another distinguishing mark betweenthe present invention and the patent cited above.

In addition to the improvement in process, the present invention offerstwo more distinct features. One of these features is the production ofquaternary ammonium alkyl sulfates in which the carbon content of theanion is exactly the same as the total carbon content in the cationY==R4. Thus through the presentinvention the production of perfectlybalanced ionics (Equionics") has become possible. In these balancedionics a still more perfect intramolecular synchronization of groups,possessing a priori desirable physical, chemical and physiologicalproperties, has been realized.

The other new feature given in the present invention is the productionof quarternary ammonium alkyl sulfates in which the alkyl radical in thesulfate group has a higher carbon content, than the total of carbonatoms present in the cationic part of the molecule (Y R4).

While some of the symmetrical quarternary ammonium alkyl sulfatedescribed in our patent application Serial No. 787,468, filed November21, 1947 (Y R4) but where the difference in carbon content between Y andR4 is very small, approximate the behavior of the products claimed inthe present invention, nevertheless these latter products differradically from the quaternary ammonium compounds of comparable carboncontent known heretofore. Usually in these latter compounds the anion isvery small in comparison to the cationic portion of the molecule. Theanion in such products is usually presented by ionizable chlorine whilethe cationic part of the molecule, in case of capillary activesubstances, contains at least 15 or more carbon atoms linked to thequaternary ammonium nitrogen atom.

Utilizing the reaction scheme presented in this invention, chemicalcompositions can be created with predetermined properties. Thus, it ispossible to produce substances in which detergency is conferred upon theanion alone or upon both, the cation and the anion. The hydrophilicaction of these types of compounds is then quite different from thecationic quaternary ammonium types of compounds possessing a dwarf sizedanionic grouping. Thus a gradual and staggered solubility behavior canbe induced in these new types of compounds claimed in the presentinvention. It is possible to produce substances ranging from completewater solubility to complete insolubility and from completely allsoluble substances to complete insolubility in non-polar solvents. Thesecharacteristics allow a wider range in practical and industrialapplications, than with detergents which incorporate surface-activityeither in the anionic part of the molecule alone (sulfonated oils,mono-alkyl sulfate salts) or only in the cationic portion of themolecule (invert soaps). Thus these new compounds are valuable aswetting, emulsifying and dispersing agents particularly in cases, whereboth the anionic as well as the cationic types, as well as the non-ionicdetergents fail. Many of thecompounds are potent germicides andfungicides.

The tertiary amines utilizable in this invention, can be of thealiphatic, aromatic, alicyclic or simple or mixed heterocyclic types.They may be plain or further substituted by hydroxyl, alkoxyl and acylgroupings. The following tertiary mines have been found perfectlysuitable for use in the present invention: tri-methyl amine; tri-ethylamine; tri-ethylol amine; the tri-propyl-, the tri-butyland tri-amylamines; N,N dimethyl amino ethanol; N,N diethylamino-ethanol;dimethyl-aniline; diethyl-, dipropyl, di-butyl, di-amyl-anilines;N,N-dimethyland N,N di ethyl benzyl amines; tri-benzylamine;N,N-dimethyland N,N-diethylalpha as well as beta naphthyl amines;N,N-dimethylcyclo-hexyl amine; N-methyl and N-ethyl-piperidine,pyridine, quinoline. iso-quinoline; nicotine and a whole series ofN-alkyl morpholines, thiamorpholines. thiamorpholine-oxides andthiamorpholine-dioxides.

Of the unsymmetrical di-alkyl sulfates the following methyl sulfateshave been used in the masses 3 chemical transformation described in thepresen invention:

Also the following methyl-cyclo-alkyl sulfates have been found useful:

Methyl-cyclohexyl- Methyl- (a-methyl) cyclohexyl- Methyl- (4t-butyl)cyclohexylflask. After thoroughly mixing the contents, the flask istightly stopper-ed and the reaction mixture heated on a steam bath at atemperature of 90 C. for a period of six hours. At the end of this timethe reaction mixture is allowed to cool and then permittedto stand atroom temperature for additional 24 hours. After this time the reactionproduct is washed with 50 cc. of ether at room temperature. The etherlayer containing any nonreacted starting materials is allowed toseparate and is then decanted off. This washing operation is once morerepeated. The etherwashed reaction product, is then recrystallized fromhot ethyl acetate. The product, N-ethyl- N,N,N-tri-n-amy1 ammoniumhexadecyl sulfate melts at 82-85 C. (uncorn).

Using the above procedure or the method given in the succeeding example,the following additional equionics were produced:

Reactants Compounds: sulfates Amine Methyl-SulfateN,N,N-'Irimethyl-N-ethyl Amman. n-amyl n-amyl N ,N,N-Trimethyl-N-ethylolAmmon. n-amyl D N ,N-Dimethyi-N,N-diethyl Ammon. n-hexyL. -n-hexy]N,N-Dimethy1-N,N-dlethyl Ammon. cyclohexyl -cyclohexyl:,N,N-Dimethyl-N,N-di-ethylol Ammon. n-hexyl Di-ethylol-methyl -n-hexyl.N,N-Dimethyl-N,N-diethyl0l Ammon. cyclohexyl .do -cyclohexy1N,N-Dimethyl-Morpho1inium n-hexyl N-Niethyi Morpholine. -n-hexyl.N-Methyl-Pyridinium n-hexyl Pyridine Do. N-Methyl-Pyridinium cyclohexyl..do -cyclohexyl. N,N-Dimethyl-Piperidinium n-heptyl N-Methyl-mpcndme.-n-hepty1. N,N,N-Tri-ethyl-N-methyl-Ammon. n-heptyl. Tn-ethyl amine Do.N,N,N-Tri-ethylol-N-methyl-Ammon. n-heptyl ri-ethyloL. Do. N-ethyl-N-ethyl-Piperidinium n-octyl N Ethy1-p1per1d -n-octylN,N,N-Trimethyl-N- henyl-Ammon. n-nonyl Dimethylanihne n-nonylN,N,N-Trimethy1-N- enzyl-Ammon. n-decyl. Benzyl -d1mcthyl. -n-decylN-Methyl-Quinolium n-decyl Qumolme Do.N,N-Diethyl-N-methyl-N-phenyl-Ammon. lauryl Diethylanilin -laury1.N,N,N-Tri-iso-amyl-N-methyl Ammon.cetyl.. Tn-iso-amyL. -oetyl. N-ethyl-N-lauryl-Piperidinium octadecyl N-Lauryl-piperidine. -octadecy1N-Methyl-N-ethyl Morpholiniu n-heptyi N-Ethyl morpholine. -n heptMethyl-(-t-amyl) cyclohexy1-; Methyl-( i-tt-octyl) cyclohexyl-sulfates.

Replacement of the methyl group in all the above cited methyl-alkylsulfates by an ethyl radical, slows down the reaction, but does notpreclude also the utilization of these types of mixed alkyl sulfates forthe preparation of types of unsymmetrical quaternary ammonium alkylsulfates claimed in this invention.

The process utilized has as its outstanding feature the choice of thereactants, i. e. a tertiary amine and a methyl-alkyl sulfate, which areheated together, in equimolar quantities, either in the presence orabsence of a suitable solvent. The procedure involved is very much thesame as described in the concomitant patent application Serial No.787,468 and in the Journal of the American Chemical Society, vol.- 70,page 618 (1948). The present invention itself as well as the pertinentreaction mechanism involved were presented before the Organic ChemistryDivision at the Chicago meeting of the American Chemical Society, inApril 1948. It was established, by independent syntheses that the shortchain alkyl radical, in the present case, the methyl group, migrates tothe nitrogen atom leaving the larger alkyl radical or cycloalkyl radicalwith the sulfate group, as illustrated above, and as is necessary forthe production of the types of compounds claimed in this invention.

Example 1.Equionics One tenth mol portion of tri-n-amyl amine (B. P.125128/l2 mm.) is mixed under warming with one tenth mol ofmethyl-n-hexadecyl sulfate (M. P. 73 C.) in a round bottomed PyrexExample 2.Carbon content of anion larger than cation One tenth mol ofN-methyl morpholine and one tenth mol of methyl-lauryl sulfate (M. P.47-48 C.) is placed into a round bottomed Pyrex flask. A water refluxcondenser is then attached to the flask and, 200 cc. of toluene added tothe reaction mixture. The mixture is then refluxed for six hours. Afterthis time, the reaction mixture is allowed to cool and is then filteredor centrifuged. The residue is then washed with 30 cc. of di-ethyl etherto remove any unreacted starting materials. After decantation of theether layer the residue is crystallized from hot ethyl acetate. Thefinal product, the N,N-dimethyl-morpholinium lauryl sulfate melts atGil-62 C. (uncorn).

Using the above procedure or the method given in the preceding example,the following N,N- dialkyl-morpholinium alkyl sulfates were prepared:

aaeasae Reacting N-alkyl-thiamorpholines, N-alkylthiamo'rpholine oxidesand N alkyl thiamorpholine-dioxides with methyl-cetyl sulfate and usingthe procedures as given in Example 1 or 3. Morphoiinium alkyl sulfatesof the following formula Clix-CH2 RI as described in Example 2 thefollowing com- N pounds were produced: cm-cfiih Compounds: CetylSulfates Amine N,N-Dimethyl-thiamorpholinium N-Methyl-thiamorpholine.N-Methyl-N-lauryl-thiamorpholinium N-Lauryl-thiamorpholine.N-Methyl-N-myristyl-thiamorpholinium. N-Myristyl-thiamorpholine.N,N,-Dimethy-thiamorpholinium oxide N-Methyl-thiamorpholine-oidde. N-Methyl-N-lauryl-thiamorpholinium oxide N -Lauryl-thiamorpholine-oxido.

N -Methy]-N-myristyl-thiamorpholinium oxideN,N-Dimethyi-thiamorpholinium-dioxideN-Methyl-N-lauryl-thiamorpholiniumdioxide.-

N-livliethyl-N-myristyl-thiamorpholinium-diox-.

N-Myristyl-thiamor holine-oxide N-Methyl-thiamorp oliue-dioxide.

N-Inuryl-thiamorpholine-dioxide.

Niglyristyl-thiamorpholine-diox- Reacting various types of tertiaryamines with methyl-lauryl sulfate under conditions as given in Examples1 and 2 the following quaternary ammonium lauryl sulfates were prepared:

Compounds: Lauryl sulphates Tert. Amine N,N,N,N,-Tetra-methyl-ammonium'Iri-methyl-amine. N,N ,N-Tri-ethyl-N nethyl-ammonmm. Tri-ethyl-amine. N,N,N-lri-ethylol-N-methyl-ammonium Tri-ethylol-emine.N-Methyl-pyridinium Pyridine. N-Methyl-piperidiniurn-. Piperidine.N-Methyl-quinolium Quinoline. N,N ,N -Irimethy1-N-phenyl-ammoniumDimethyl-anilme. N,N-Di-ethyl-N-methyl-N-phenyl-ammonium Diethyl-amline.N,N,N-Trimethyl-a-naphthyl-ammonium. Dimethyl-a-naphthyl amine.N,N,N-Trimethyl-fl-naphthyl-ammonium Dimethyl-fl-naphthyl amine.

What we claim is: 1. Quarternary ammonium alkyl sulfates of thefollowing formula:

wherein, R1, R2 and R: represent organic residues of which at least twomay form together with the nitrogen atom a heterocyclic nucleus, R4 andY represent alkyl groups, the number of carbon atoms present in thealkyl group Y being at least equal to the sum of the number of carbonatoms present in the cation.

2. Quaternary ammonium alkyl sulfates of the following formula CHz-CH:R;

wherein R1 and R2 represent alkyl groups and Z a member of the groupconsisting of O-, -S-, SO, and SO2-, while Y is an alkyl group differentfrom the alkyl groups R1 and R2 as well as from the group CH CH andwherein the number of carbon atoms present in the alkyl group Y is atleast equal to the sum of the number of carbon atoms present in thealkyl groups R1 and R2 and the group CHr-CHrwherein R1 and R: representalkyl groups while Y is an alkyl group different from thegroups R1 andR2 and the group 4. N,N-dimethyl morpholinium cetyl sulfate of thefollowing formula 5. N,N-dimethyl morpholinium n-hexyl sulfate of thefollowing formula 6. N-methyl-N-lauryl morpholinium octadecyl sulfate ofthe following formula CHQCH! CH3 7. Thiamorpholinium alkyl sulfates ofthe following formula:

CHzCH! cinch, Ra

wherein R1 and R2 represent aliryl groups, while Y is an alkyl grouphaving a number of carbon atoms at least equal to the sum of the numberof carbon atoms in the alkyl groups R1 and R2 and the group CHaCHr- 8.Pyridinium allryl sulfates of the following formula:

comprising reacting at elevated temperature a tertiary amine of theformula with an unsymmetrical dialkyl sulfate of the formula R4O.SOz.OY,wherein R1, Ra, Ra, represent organic residues of which at least two mayform together with the nitrogen atom a heterocyclic nucleus. while R4,and Y are alkyl groups, the number of carbon atoms present in the alkylgroup Y being at least equal to the sum of the number of carbon atomspresent in the tertiary amine and in the alkyl group R4, and Y beingdifferent from the alkyl group R4 and from any alkyl group present insaid tertiary amine.

10. A process of producing quaternary ammonium alkyl sulfates of thefollowing formula a iz.

comprising reacting at elevated temperature a tertiary amine of theformula with an unsymmetrical dialkyl sulfate of the formula R4O.SO2.OY,wherein R1, R2, and R3 represent alkyl groups of which at least two mayform together with the nitrogen atom a heterocyclic nucleus, while R4and Y are alkyl groups, the number of carbon atoms present in the alkylgroup Y-being at least equal to the sum of the number of carbon atomspresent in the alkyl groups R1, R2, R3, and R4, and Y being differentfrom any of the alkyl groups R1, R2, R3, and R4.

11. A process of producing quaternary ammonium sulfates of the followingformula cllrglka comprising reacting at elevated temperature a tertiaryamine of the following formula CHz-CH: R1

, wherein R1 represents an alkyl group and Z is a member of the groupconsisting of O--, S--, 40-, and SO2, with an unsymmetric dialkylsulfate of the formula 12.20.802.01 wherein R2 and Y are alkyl groups,the number of carbon atoms present in the alkyl group Y being at leastequal to the sum of the number of carbon atoms present in the alkylgroups R1 and R2 and the group CHz-CHQ- and Y being different from anyof the groups R1 and R2 and the group 12. A process of producingmorpholinlum alkyl sulfates of the following formula CHr-CH: R1 0 lllo.so,.oY1-

CH( zI i1 comprising reacting at elevated temperature a morpholinecompound of the formula wherein R1 is an alkyl group, with anunsymmetrical dialkyl sulfate of the formula wherein R2 and Y are alkylgroups, the number of carbon atoms present in the alkyl group Y being atleast equal to the sum of the number of carbon atoms present in thealkyl groups R1 and R2 and the group 13. A process of producingthiamorpholinium alkyi sulfates of the following formula comprisingreacting at elevated temperature a thiamorpholine compound of theformula CHzCH: R1 S CH:CH|

wherein R1 is an alkyl group, with an unsymmetrical dialkyl sulfateofthe formula R2O.SO:.OY

wherein R2 and Y are alkyl groups. the number of carbon atoms presentin' the alkyl group Y being at least equal to the sum of the number ofcarbon atoms present in the alkyl groups R1 and R2 and the group CHICHr-S\' CHaCHz- JOSEPH B. NIE'DERL. WILLIAM F. HART. MARTIN E. MCGREAL.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Schonhofer et a1. May 26, 1936 Bertsch eta1 Jan. 11, 1938 Number Number 10 Name Date Bruson Apr. 26, 1938 GuntherSept. 20, 1938 Hahl et a1 Mar. 28, 1939 Epstein Oct. 24, 1939 Harris May21, 1940 Wibaut et a] June 24, 1941 Bertsch Sept. 23, 1941 Munz et a1.Feb. 3, 1942 Niederl et al. July 10, 1945 MacMullen et a1. Feb. 19, 1946FOREIGN PATENTS Country Date France Apr. 10, 1933 OTHER REFERENCESShelton, Jour. Am. Chem. Soc., vol.'68 (1946)

1. QUATERNARY AMMONIUM ALKYL SULFATES OF THE FOLLOWING FORMULA: